Economic evaluation and budget-impact of accelerated partial breast irradiation (APBI) versus standard or hypofractionated whole breast irradiation (WBI) in postmenopausal women with early-stage breast cancer. Results from the French SHARE randomized trial.

PURPOSE: This economic evaluation reports the incremental cost-utility ratio and national budget impact in France of accelerated partial breast irradiation (APBI) vs standard or hypofractionated whole breast irradiation (WBI) in breast cancer patients at low risk of local recurrence. MATERIALS AND METHODS: We compared 490 women randomized to the APBI (ten fractions delivered twice daily over one week) with 488 women in the WBI arm (one fraction per day delivered five days per week over three or six weeks). We took the perspective of the French national health insurance with a three-year time horizon. The outcome was quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was estimated and uncertainty was explored by probabilistic bootstrapping. Transportation and sick leave costs were added in a sensitivity analysis and a national budget impact analysis based on the incidence of breast cancer estimates in France performed. RESULTS: At three years, the average cost per patient was €2,549 (±1,954) in the APBI arm and €4,468 (±1,586) in the WBI arm (p-value < 0.001), radiotherapy was the main driver of the difference between the two arms. No significant difference was found in QALYs. For an average of 60,000 new cases of breast cancer diagnosed annually in France, 28,000 would be eligible for treatment with APBI. A 100% uptake of APBI would result in a yearly30 million€ cost saving. CONCLUSION: APBI for the treatment of postmenopausal women with early-stage breast cancer is cost saving, with no difference in outcome measured by QALYs.

Radiation-induced lung injury after breast cancer treatment: incidence in the CANTO-RT cohort and associated clinical and dosimetric risk factors.

Purpose: Radiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limited further improvement. The aim of our study was to assess the incidence of RILI in current practice and to determine clinical and dosimetric risk factors associated with RILI occurrence. Material and methods: Data from 3 out of the 10 top recruiting centers in CANTO-RT, a subset of the CANTO prospective longitudinal cohort (NCT01993498), were retrospectively analyzed for RILI occurrence. This cohort, which recruited invasive cT0-3 cN0-3 M0 breast cancer patients from 2012 to 2018, prospectively recorded the occurrence of adverse events by questionnaires and medical visits at the end of, and up to 60 months after treatment. RILI adverse events were defined in all patients by the association of clinical symptoms and compatible medical imaging. Results: RILI was found in 38/1565 (2.4%) patients. Grade II RILI represented 15/38 events (39%) and grade III or IV 2/38 events (6%). There were no grade V events. The most frequently used technique for treatment was 3D conformational RT (96%). In univariable analyses, we confirmed the association of RILI occurrence with pulmonary medical history, absence of cardiovascular disease medical history, high pT and pN, chemotherapy use, nodal RT. All dosimetric parameters were highly correlated and had close predictive value. In the multivariable analysis adjusted for chemotherapy use and nodal involvement, pulmonary medical history (OR=3.05, p<0.01) and high V30 Gy (OR=1.06, p=0.04) remained statistically significant risk factors for RILI occurrence. V30 Gy >15% was significantly associated with RILI occurrence in a multivariable analysis (OR=3.07, p=0.03). Conclusion: Our study confirms the pulmonary safety of breast 3D RT in CANTO-RT. Further analyses with modern radiation therapy techniques such as IMRT are needed. Our results argue in favor of a dose constraint to the ipsilateral lung using V30 Gy not exceeding 15%, especially in patients presenting pulmonary medical history. Pulmonary disease records should be taken into account for RT planning.

CANTO-RT: One of the Largest Prospective Multicenter Cohort of Early Breast Cancer Patients Treated with Radiotherapy including Full DICOM RT Data.

This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received RT in one of the 10 top recruiting CANTO centers were selected. Individual full DICOM RT files were collected, pseudo-anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform. CANTO-RT included 3875 BC patients with a median follow-up of 64 months. Among the 3797 patients with unilateral RT, 3065 (80.4%) had breast-conserving surgery, and 2712 (71.5%) had sentinel node surgery. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%), including internal mammary chain in 844 patients (21.8%). Most patients (3691 (95.3%)) were treated with 3D conformal RT. Target volumes, organs at risk contours and dose/volume histograms were extracted after quality-control procedures. CANTO-RT is one of the largest early BC prospective cohorts with full individual clinical, biological, imaging and DICOM RT data available. It is a valuable resource for the identification and validation of clinical and dosimetric predictive factors of RT and multimodal treatment-related toxicities.

Impact of radiation therapy on fatigue at 1 year in breast cancer survivors in the prospective multicentre CANcer TOxicity cohort.

BACKGROUND: Fatigue is a common and disabling symptom after breast cancer (BC) treatment, significantly impacting patients' quality of life. We aimed to assess the impact of radiation therapy (RT) modalities on fatigue one year after treatment among patients with early-stage BC. METHODS: We used CANTO-RT, a subcohort of CANcer TOxicity (CANTO; NCT01993498), a multicentric nationwide prospective cohort of stages I-III BC treated from 2012 to 2017. Our primary outcome was severe global fatigue 1 year after RT completion (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 score ≥40/100). The secondary outcomes included severe physical, emotional and cognitive fatigue (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-FA12). RT-related variables were used as independent variables. Multivariable logistic regression models assessed associations between RT-related variables and fatigue. RESULTS: The final analytic cohort included 3295 patients. The prevalence of severe global fatigue 1 year after treatment was 33.3%. Internal mammary chain RT (adjusted odds ratio [OR] 1.48 [95% confidence interval [CI] 1.03-2.13; p = 0.0355]) and normofractionated RT (adjusted OR 1.88 [95% CI 1.06-3.31; p = 0.0298]) were associated with increased odds of severe global fatigue. In addition, there was a significant association between normofractionated RT (adjusted OR 1.849 [95% CI 1.04-3.3; p = 0.0354]) and an increased likelihood of severe physical fatigue. CONCLUSION: We found a significant association between internal mammary chain RT (versus No), normofractionated RT (versus hypofractionated RT) and increased likelihood of persistent severe global fatigue. Our data add to the current understanding of treatment-related factors affecting fatigue after BC and could lead to personalised interventions to improve the prevention and management of this disabling symptom.

Prospective evaluation of intensity-modulated radiotherapy toxicity in extremity soft tissue sarcomas patients: A role for irradiated healthy soft tissue volume?

AIM: To prospectively assess toxicities of curative-intent intensity-modulated conformal radiotherapy (IMRT) in patients with extremity soft tissue sarcomas (ESTS). METHODS: Data from 59 consecutive patients with ESTS between 2014 and 2019 were both retrospectively and prospectively analysed. Toxicity data were collected both by confidential mailed survey (39% completed) and medical charts, and graded according to CTCAE v5.0. Normal tissues dosimetric data (healthy soft tissue segment, joint and bone) were included. The healthy soft tissue segment was created by adding 5 cm on either side of the PTV on CT axial slices, the PTV and bone (and articulation if present) were then removed from the generated volume. RESULTS: IMRT was delivered post-operatively for nearly half of patients (n = 24, 41%), preoperatively for 18 (31%) and exclusively for 17 (28%; salvage: 13% or immediately inoperable: 15%). The median total dose delivered to the planned target volume (PTV) was 50.4 Gy (36-68 Gy) and 13 patients (22%) received a boost. With a median follow-up of 27 months (6-94 months), a total of 87 late effects were identified in 44/59 (75%) patients: 89% G1-2, and 11% G3-4. The main G1-2 toxicities were: functional limitation (36%), oedema (29%), gait disorders (20%), neurological disorders (20%) and chronic pain (32%). G3-4 toxicities were pain (n = 2), arterial stricture (n = 1) and a chronic wound requiring skin graft (n = 2). No bone fracture was observed. Quality of life was rated as good or very good in 70% patients who completed the survey. Larger (>3500 cm3) healthy soft tissue segment volume was associated with decreased late toxicities (p = 0.02). No other predictive factor of toxicity was identified. The 2-year rates of local control, overall survival and recurrence-free survival were 90%, 90% and 64%, respectively. CONCLUSION: Healthy soft tissue segment volume influenced toxicity. Long-term prospective monitoring in a homogeneous population remains critical to assess the impact of IMRT induced chronic toxicity in ESTS patients. This should ideally lead to a validated normal tissue dose constraint (e.g.: healthy soft tissue segment volume > 3500 cm3) to recommend for practitioners to help reduce the late toxicity risk.

Tumour motion management in lung cancer: a narrative review.

Respiratory motion is one of the geometrical uncertainties that may affect the accuracy of thoracic radiotherapy in the treatment of lung cancer. Accounting for tumour motion may allow reducing treatment volumes, irradiated healthy tissue and possibly toxicity, and finally enabling dose escalation. Historically, large population-based margins were used to encompass tumour motion. A paradigmatic change happened in the last decades led to the development of modern imaging techniques during the simulation and the delivery, such as the 4-dimensional (4D) computed tomography (CT) or the 4D-cone beam CT scan, has contributed to a better understanding of lung tumour motion and to the widespread use of individualised margins (with either an internal tumour volume approach or a mid-position/ventilation approach). Moreover, recent technological advances in the delivery of radiotherapy treatments (with a variety of commercial solution allowing tumour tracking, gating or treatments in deep-inspiration breath-hold) conjugate the necessity of minimising treatment volumes while maximizing the patient comfort with less invasive techniques. In this narrative review, we provided an introduction on the intra-fraction tumour motion (in both lung tumours and mediastinal lymph-nodes), and summarized the principal motion management strategies (in both the imaging and the treatment delivery) in thoracic radiotherapy for lung cancer, with an eye on the clinical outcomes.

Five-Year Results of the Preoperative Accelerated Partial Breast Irradiation (PAPBI) Trial.

PURPOSE: In this multicenter phase 2 feasibility study, we investigated the impact of preoperative accelerated partial breast irradiation (PAPBI) on local control, breast fibrosis, and cosmetic outcome. METHODS AND MATERIALS: Women aged >60 years with an invasive, unifocal (mammography and magnetic resonance imaging), nonlobular adenocarcinoma of the breast were treated with PAPBI. Six weeks after radiation therapy, a wide local excision was performed. Radiation therapy consisted of 10 × 4 Gy (2010-2013) or 5 × 6 Gy (after 2013) to the tumor (gross target volume) with a 25 mm margin (20 mm from gross target volume to clinical target volume, 5 mm planning target volume). RESULTS: One hundred thirty-three patients treated between 2010 and 2016 were analyzed with a median follow-up of 5.0 years (0.9-8.8 years). Seventy-eight (59%) patients were treated with 10 × 4 Gy in 2 weeks and 55 (41%) patients with 5 × 6 Gy in 1 week. Eighteen postoperative complications (14%) occurred in 15 patients (11%). The proportion of patients with no to mild fibrosis in the treated part of the breast at 2 years and later time points was around 90%. Cosmesis improved over time in several patients: excellent to good cosmetic score as rated by the physician was 68% at 6 months and 92% at 5 years. Seventy-seven percent (6 months) to 82% (5 years) of patients were "satisfied" or "very satisfied" with their cosmetic outcome. Three recurrences were detected in the biopsy track and 1 recurrence in the ipsilateral breast. CONCLUSIONS: PAPBI is a feasible method with a low postoperative complication rate, limited fibrosis, and good to excellent cosmetic outcome. The local recurrence rate was 3% at 5 years; however, no local recurrences were observed since removal of the needle biopsy track.

Evaluation of MVCT imaging dose levels during helical IGRT: comparison between ion chamber, TLD, and EBT3 films.

The purpose of this investigation was to evaluate the dose on megavoltage CT (MVCT) images required for tomotherapy. As imaging possibilities are often used before each treatment and usually used several times before the session, we tried to evaluate the dose delivered during the procedure. For each scanning mode (fine, normal, and coarse), we first established the relative variation of these doses according to different technical parameters (explored length, patient setup). These dose variations measured with the TomoPhant, also known as Cheese phantom, showed the expected variations (due to the variation of scattered radiation) of 15% according to the explored length and ± 5% according to the phantom setup (due to the variation of the point of measurement in the bore). In order to estimate patient doses, an anthropomorphic phantom was used for thermoluminescent and film dosimetry. The degree of agreement between the two methods was very satisfactory (the differences correspond to 5 mGy per imaging session) for the three sites studied (head & neck, thorax, and abdomen). These measurements allowed us to estimate the delivered dose of between 1 cGy and 4 cGy according to the site and imaging mode. Finally, we attempted to investigate a way to calculate this delivered dose in our patients from the study conducted on a cylindrical phantom and by taking into account data from the initial kV-CT scan. The results we obtained were close to our measurements, with discrepancies below 5 mGy per MVCT.

SHARE: a French multicenter phase III trial comparing accelerated partial irradiation versus standard or hypofractionated whole breast irradiation in breast cancer patients at low risk of local recurrence.

The standard treatment for breast cancer patients at low risk of recurrence is based on conservative surgery followed by radiation therapy delivered to the whole breast. The accelerated partial breast irradiation (APBI) concept, developed more than 15 years ago, could be an option in selected patients. However, the ideal patient profile for APBI is still not clearly identified. Recent reports from the American Society for Radiation Oncology (ASTRO) and the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) have suggested selection criteria for "suitable patients" who could receive APBI outside of clinical trials. Currently, there are 6 ongoing phase III trials. All are characterized by a significant heterogeneity regarding inclusion criteria and stratification factors. The French UNICANCER trial (SHARE; ClinicalTrials.gov identifier NCT01247233) will randomize 2,800 patients in 3 arms: APBI (1 week) using 3-dimensional (3D) conformal radiotherapy, standard radiotherapy (6.5 weeks), and hypofractionated radiotherapy (3 weeks). In this article, we review the reported retrospective studies as well as older randomized trials. We will also describe the differences between the 6 ongoing phase III trials and the particularities of the French SHARE trial.